The document WO 95/22319 describes a method for making by extrusion/spheronization fine particles based on an active principle. The fine particles obtained have a size of between 50 μm and 1 mm. In particular, the examples describe particles having a size equal to 300 μm, comprising up to 72% of active principle in the presence of at least three excipients including in particular an extrusion agent. In addition, these same examples and in particular formula 1 c shows that this method does not make it possible to obtain fine particles of this order of size with a high concentration of active principle, equal to 95%. Finally, the fine particles obtained at the end of the method have a surface which is too irregular to allow subsequent satisfactory treatment, the coating designed to mask the taste of the active principle requiring, for example, a high level of coating.
The document EP-A-443572 describes a coating composition which can be applied in various forms and in particular microgranules designated here by the expression “fine granules”. It is indicated that at least 75% of the population of microgranules have a size of between 1 and 500 μm. No information is given relating to the concentration of active principle in the microgranule.
The document FR-A-2 419 722 describes microgranules of active principle and in particular of ferritin and their method of preparation. These microgranules consist of a core comprising a first coating obtained by spraying an aqueous suspension of active principle, the cohesion of said first coating with the core being brought about by uniform dispersion, between each spraying step, of small quantities of talc (see in particular page 7, example 3). The core thus coated has, in addition, a second coating, whose nature depends on the characteristics of release of the desired active principle. In practice, the core itself can have two different forms. Thus, in a first embodiment, the core consists exclusively of inert material, for example of the sucrose type. In a second embodiment, (example 3), the core exists in the form of a granule based on a binder (for example starch) and an active principle in ratios of 50/50.
The method of manufacture and the microgranule thus obtained exhibit a number of disadvantages. As regards first of all the method of manufacture, it requires at least four steps, which are the manufacture of the core, and then, alternatively, the application of the first coating, and of the talc dispersion and finally the application of the second coating. Such a method is particularly long and cannot be performed continuously. In addition, the cohesion of the first coating onto the core is not always homogenous, leading to coated cores having an irregular surface and thereby increasing the quantity of material necessary for the second coating. As regards the microgranule as such, it is indicated that the core before coating has a size of between 0.3 and 0.5 millimeters (see examples) for a concentration of active principle representing only 50% of the mass of the core.
Accordingly, the first problem which the invention proposes to solve is to provide microgranules whose core, before coating of the functional layer(s) conferring on the microgranule the desired characteristics of release of the active principle and/or of masking the taste, is as concentrated as possible in active principle.
The second problem which the invention proposes to solve is to provide a microgranule whose nucleus, before coating the functional layer(s), is appreciably spherical so as to reduce its specific surface and thus reduce the quantity of material necessary for subsequent coating.
The third problem which the invention proposes to solve is to provide a microgranule whose nucleus, before coating the functional layer(s), has a size which is as small as possible, advantageously a median size of less than 500 μm.